This phase II trial tests how well concentrating heated (hyperthermic) chemotherapy in the area that contains the abdominal organs (intraperitoneal [IP]) at the time of surgery works in treating patients with gastric or gastroesophageal junction adenocarcinoma at high risk of the cancer coming back to the abdominal cavity (peritoneal) after a period of improvement (recurrence). Recurrence in the peritoneum often occurs within the first 18 months after surgery. This is thought to be due to tumor cells that may scatter and spread during surgery. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Paclitaxel alone and in combination with other chemotherapy agents have been shown to be effective treatments for gastric tumors. However, systemic delivery of these drugs has not been shown to be effective in treating peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a procedure that involves the infusion of a heated chemotherapy solution, such as cisplatin and paclitaxel, that circulates into the abdominal cavity. Giving HIPEC with cisplatin and paclitaxel at the time of surgery may reduce peritoneal recurrence in patients with gastric or gastroesophageal junction adenocarcinoma at high risk.

Inclusion Criteria:

• Age ≥ 18 and ≤ 80 years
• Histological confirmation of adenocarcinoma of the stomach or gastroesophageal junction (GEJ) (Siewert type II or III)
• Tumor index (TI) ≥ 90 (T stage multiplied by the largest tumor diameter in mm on endoscopic ultrasound [EUS]). Patients with linitus plastica automatically have TI ≥ 90
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1000/mm^3
• Platelet count ≥ 75,000/mm^3
• Calculated creatinine clearance ≥ 60 ml/min using the Cockcroft-Gault formula
• No radiographic or histological evidence of distant metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Willingness to provide mandatory blood specimens for correlative research
• Willingness to provide mandatory tissue specimens for correlative research
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Renal insufficiency (estimated glomerular filtration rate [eGFR] < 60)
  • Or psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Active second malignancy currently receiving systemic treatment ≤ 6 months prior to pre-registration

• History of myocardial infarction ≤ 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias